In utero tumor development and identification ofCTNNB1 mutation in a newborn case of ossifying renal tumor of infancy Shin Kasai1, Minori Tamai1, Eiji Sugihara2, Naoki Oishi3, Kyoko Hinata1, Koshi Akahane1, Kumiko Goi1, Yuko Hata2, Tetsuo Kondo3, Takahiko Mitsui4, Mio Tanaka5, and Takeshi Inukai1*1) Departments of Pediatrics, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan2) Division of Gene Regulation, Cancer Center and Open Facility Center, Research Promotion Headquarters, Fujita Health University School of Medicine, Toyoake, Aichi, Japan3) Department of Pathology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan4) Department of Urology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan5) Department of Pathology, Kanagawa Children’s Medical Center, Yokohama, Japan.*Corresponding authorTakeshi Inukai, Department of Pediatrics, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409–3898, Japan. Email: tinukai@yamanashi.ac.jpWord count: 849/850 wordsFigures: 2Supplemental Tables: 2Supplemental Figures: 5Running title: CTNNB1 mutation in ossifying renal tumor of infancy (44/50 characters)Key words: CTNNB1, Ossifying renal tumor of infancy, β-catenin, hematuria, calcification, renal tumorAn abbreviations keyORTI: Ossifying renal tumor of infancyWES: Whole exome sequencingEMA: Epithelial membrane antigenPBMC: Peripheral blood mononuclear cellsCNV: Copy number variationILNR: Intralobar nephrogenic restCNSET: Calcifying nested stromal-epithelial tumor

Metastatic intrathyroid thymic carcinoma (ITTC) is a rare cancer that has no effective drugs. Herein, we report that comprehensive cancer mutation analysis revealed amplification of CD274 gene encoding PD-L1. Multiplex immunohistochemistry also clarified the presence of an immunosuppressive microenvironment via a PD-1/PD-L1 pathway in metastatic ITTC.